What is REALLY going on in MPNs? Real-world evidence in MPNs.
“We need to have a more objective approach to trying to assess [MPN patients’] symptom burden and making therapeutic decisions.”
Professor Adam Mead
MF is a chronic form of blood cancer
Progression of MF is characterised by an increase in collagen fibrosis in the bone marrow and defined by grades of marrow fibrosis:1
- MF1 (reticulum)
- MF2 (collagen fibrosis)
- MF3 (osteosclerosis)
Grade 2 or 3 fibrosis is associated with an increase in disease burden and possible progression.2
Histopathologically, primary MF is characterised by increased cellularity with granulocytic proliferation, and clusters of megakaryocytes of various sizes, with hypolobated or irregular nuclei.3
The burden faced by patients with MF falls into four main categories:4
- Enlarged spleen and associated complications
- Abnormal blood counts (cytopenias and anaemia)
- Systemic symptoms
- Decreased life expectancy
Using a validated MPN symptom assessment form allows a quantitative assessment of:7
- symptom burden
- disease progression
- treatment response
The MPN10 score tracks ten distinct symptoms:7 fatigue, early satiety, abdominal discomfort, inactivity, concentration problems, night sweats, itching, bone pain, fever and weight loss.
Using these scores helps to define the clinical burden of MF in individual patients; the severity of symptoms can be high even in patients classified as being low risk.8,9
Here, Professor Adam Mead describes how the application of these symptom tracker tools has revealed the disease burden of patients in different risk categories
In the COMFORT I and COMFORT II trials, ruxolitinib was shown to be superior to placebo and best available therapy for reducing total symptom score and for decreasing spleen volume.10,11
In the webinar, Professor Adam Mead shared advice, based on his personal experience and on current guidelines, for the use ruxolitinib in practice, including:
- Dose optimisation is important12
- Patient should be screened for tuberculosis, hepatitis B and other infections before therapy is commenced.13,14
- Early cytopenias may be observed. Anaemia is common but usually resolves within 3 months, and can be treated as necessary.10 Infections are also possible14
- Cytopenias can also arise as later onset effects, in which case the possibility of progression or other potential causes should be considered12,14
In this clip, Professor Adam Mead describes his “grand scheme” for the management of patients with MF, from diagnosis, through assessment and prognostication, to therapeutic goals
The REALISM real-world evidence study showed:
- Reporting/recording of prognostic scores is low (16%)15
- Active treatment is started in 53% of patients at diagnosis, with 47% of patients on watch-and-wait approaches15
- 23% of patients are started on hydroxyurea, and 17% on ruxolitinib15
- 47/200 patients died during the course of the study; 38% of these deaths were disease-related15
Here, Professor Adam Mead discusses the most common first management strategies used for patients with myelofibrosis
The TRACK survey investigated the implementation and interpretation of the BSH guidelines for the diagnosis and management of MF across the UK.16 42 healthcare professionals from district general hospitals or tertiary centres were interviewed in 2018, with the following results:16
- Usage of guidelines: 98% of physicians used the BSH guidelines to support management of patients with MPNs, with 60% using more than one set of guidelines
- Next generation sequencing (NGS) myeloid panel testing: 88% of physicians have access to an NGS panel or equivalent; however, 64% would like further education in interpreting the results
- Prognostic tools: DIPSS is the most commonly used prognostic scoring system, followed by DIPSS+ and IPSS
- Symptom assessment tools: 52% of physicians used a symptom assessment tool to assess changes in constitutional symptoms, with the MPN10 tool the most commonly used (79%)
- Anaemia management: first-line treatment for anaemia was erythropoietin-stimulating agents in 71% of cases, and transfusions in 38% of cases
- Spleen size measurement: 80% of physicians measured the spleen size at diagnosis. All physicians used palpation to measure the spleen, with 48% also using ultrasound.
86% of physicians answered “yes” to the question: “Do you think the BSH guidelines should be revised?”
In this clip, Professor Adam Mead explains the rationale behind the TRACK real-world study
BSH, British Society for Haematology; DIPSS, dynamic international prognostic scoring system; IPSS, international prognostic scoring system.
- Thiele J, Kvasnicka H M et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005;90(8):1128–1132.
- Guglielmelli P, Rotunno G, Pacilli A, et al. Prognostic impact of bone marrow fibrosis in primary myelofibrosis. A study of the AGIMM group on 490 patients. Am J Hematol. 2016;91(9):918-922.
- Tefferi A, Thiele J et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007;110 (4):1092–1097.
- Cervantes F, Dupriez B et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009;113(13):2895–2901.
- Harrison C N, Koschmieder S et al. The impact of myeloproliferative neoplasms (MPNs) on patient quality of life and productivity: results from the international MPN Landmark survey. Ann Hematol 2017;96(10):1653–1665.
- Mesa R A, Miller C B et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients' overall health and productivity: the MPN Landmark survey. BMC Cancer 2016;16:167.
- Emanuel R M, Dueck A C et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 2012;30(33):4098–4103.
- Mesa R, Miller C B et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients' overall health and productivity: the MPN Landmark survey. BMC Cancer 2016;16:167.
- Geyer H L, Mesa R A et al. Therapy for myeloproliferative neoplasms: when, which agent, and how? Clinical trials & observations. Blood 2014;124(24):352–3537.
- Verstovsek S, Mesa R A et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366(9):799–807.
- Harrison C, Kiladjian J J et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366(9):787–798.
- Verstovsek S, Golitb J et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. Onco Targets Ther 2014;7:13–21.
- Reilly J T, McMullin M F et al. Use of JAK inhibitors in the management of myelofibrosis: a revision of the British Committee for Standards in Haematology guidelines for investigation and management of myelofibrosis 2012. Br J Haematol 2014;167(3):418–420.
- JAKAVI® (ruxolitinib) Summary of Product Characteristics.
- Mead A J, Butt N et al. A retrospective real-world evidence study to review the current treatment pathways for myelofibrosis from across the UK (the REALISM UK study). Presented at British Society for Haematology 59th Annual Scientific Meeting, Glasgow, UK, 1-3 May 2019; OR–008.
- Harrison C N, Mead A J et al. A physician survey on the application of the British Society for Haematology guidelines for the diagnosis and management of myelofibrosis in the UK. Br J Haematol 2020;188(6):e105–e109.